title: Cytokine regulation of human microglial cell IL-8 production.
abstract: IL-8 involvement in neutrophil activation and chemotaxis may be important in inflammatory responses within the central nervous system, secondary to meningitis, encephalitis, and traumatic injury. The source of IL-8 within the brain during these inflammatory processes, however, is unknown. To explore the role of microglia in the production of IL-8, human fetal microglia, which are the resident macrophages of the brain, were treated with LPS and pro- and anti-inflammatory cytokines to determine their effects on IL-8 production. We found that IL-8 protein levels increased in response to LPS or IL-1 beta, or to TNF-alpha, which also corresponded to elevated IL-8 mRNA levels by RT-PCR. Pretreatment with IL-4, IL-10, or TGF-beta 1 potently inhibited the stimulatory effects of these proinflammatory agents. These findings indicate that human microglia synthesize IL-8 in response to proinflammatory stimuli, and that anti-inflammatory cytokines down-regulate the production of this chemokine. These results may have important therapeutic implications for certain central nervous system insults involving inflammation.
authors.affiliation: Neuroimmunobiology and Host Defense Laboratory, Minneapolis Medical Research Foundation, MN 55404, USA.
authors.forename: L C
authors.initials: LC
authors.lastname: Ehrlich
authors.forename: S
authors.initials: S
authors.lastname: Hu
authors.forename: W S
authors.initials: WS
authors.lastname: Sheng
authors.forename: R L
authors.initials: RL
authors.lastname: Sutton
authors.forename: G L
authors.initials: GL
authors.lastname: Rockswold
authors.forename: P K
authors.initials: PK
authors.lastname: Peterson
authors.forename: C C
authors.initials: CC
authors.lastname: Chao
mesh_terms: D000367:Age Factors; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D005333:Fetus; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000276:immunology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4